A significant increase in Mr2 expression and in CM contractility after exposure to a cholinergic agonist is detected in 30 days treated rats. Ultrastructural studies have already demonstrated that the CM of the rat proximal colon is subdivided in an inner and outer portion differing in morphology and size of their SMC. However, to date no information was available on possible differences in the expression of specific markers between the two portions. The present data showed that the SMC of the icl are particularly thin, possess several branches by which they contact each other forming a dense network, and are richer in SER, caveolae, Cav-1, aSMA and Mr2 than the SMC of the ocl. The intense Cav-1-IR is likely related to the richness in caveolae. The intense aSMA-IR might depend on the high content in the thin contractile Dilmapimod filaments that fill the icl cell cytoplasm. The intense Mr2-IR likely indicates the icl cells are a preferred NIBR189 target of the neighbouring nerve endings, many of which are ChAT-IR. Conversely, the expression of calret, calseq and eNOS is similar between the icl and ocl cells. Reasonably, all these features should reflect a peculiar role of the icl in colonic contractility. Presently, we do not have enough data to identify this role and we can only make some hypotheses. The contacts with the submucosal ICC, i.e. the colonic pacemaker cells, and the richness in Mr2 make the icl cells the first target of the ICC electrical activity and excitatory inputs, respectively. When one or both of these inputs trigger the icl, it contracts forming a tight ring able to favour, from one side, the water and electrolyte absorption, and from the other side, together with the outer portion, the progression of the semisolid content present in the proximal colon. In the rats chronically treated with OB a consistent increase in caveolae and SER, already appreciable at 10 days, was seen in the CM, especially in the icl. Moreover, a peculiar peripheral distribution of mitochondria in all the CM cells and an increase in specialized cell-to-cell contacts in the ocl were present following 30 days of OB treatment.